Alternative botanical therapies for menopausal symptoms are becoming more widely used, in part due to recent reports from the Women's Health Initiative (WHI) that combined estrogen and progestin therapy increases risks for breast cancer, stroke, and cardiovascular disease. The National Center for Complementary and Alternative Medicine (NCCAM) Fiscal Year 2003 Research Priorities advocate both clinical studies evaluating the efficacy of botanical therapies for menopausal symptoms and clinical studies elucidating their mechanisms of action, optimally through collaborative randomized clinical trials. This Mentored Scientist Development Award (K01) application focuses on developing the principal investigator's ability to become an independent investigator of the mechanisms by which complementary and alternative therapies affect brain function. There is a pressing need for skilled clinical investigators with advanced training to meet those priorities. This candidate brings to this training effort uncommon expertise and research experience in sex steroid hormones, cognition, and brain function - including co-development of the WHI Study of Cognitive [unreadable] Aging - as well as active collaborations with investigators at the URIC/NIH Center for Botanical Dietary [unreadable] Supplement Research in Women's Health. The active research component of the proposed training program will initially focus on the mechanisms by which black cohosh and red clover affect neurocognitive function and mood. The specific mentored activities of this Award focus on a three-pronged training program to develop the principal investigator's ability to investigate the neural, physiological, and neurochemical mechanisms of action of botanical therapies on the CNS. The first activity focuses on functional magnetic resonance imaging and diffusion tensor imaging to examine the influence of botanicals on the brain systems underlying memory performance. The second activity focuses on the use of ambulatory sternal skin conductance monitors in the measurement of hot flushes to investigate whether botanicals improve cognition by improving menopausal symptoms. The third activity involves implementation of pharmacological challenge methods to examine whether botanical therapies act through serotonin to influence CNS function. The long-term goal of this training experience is to provide the protected time and training for the PI to develop readily generalizable skills for investigating a range of botanical therapies on cognitive function, especially extracts identified by the Center's basic science program as having potential beneficial effects on the CNS. The proposed research program builds on the UIC/NIH Botanical Center's comprehensive program of basic and clinical research and extends its clinical research program in a new and timely direction. The lack of understanding of the effects of botanical therapies on brain function and the basic mechanisms by which alternative therapies can influence cognition both underscore the need to train researchers with the necessary skills to advance clinical research in this area and address pressing needs in women's health research. [unreadable] [unreadable]